Recurrent Renal Stones Research Articles

Histomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide

Twenty-seven normocalcemic patients aged 11-69 yrs with recurrent renal stone formation and idiopathic hypercalciuria were studied before and after treatment with hydrochlorthiazide (TD) 50 mg twice a day for 6 months. Hypercalciuria was defined as a 24 h renal calcium excretion of more than 7.5 mmol for males and 6.3 mmol for females. Quantitative histomorphometric analysis of iliac crest bone biopsies were performed before and after treatment. TD treatment increased the adjusted serum calcium level (p less than 0.01), whereas no significant effects on the serum levels of phosphorous, alkaline phosphatase or iPTH were found. The urinary calcium/creatinine ratio decreased (p less than 0.01) during TD treatment, whereas no change in the urinary phosphorous/creatinine ratio was found. The histomorphometric analysis revealed a reduction in the extent of eroded surfaces (p less than 0.05) and bone formation rate (p less than 0.05) as well as a decrease in the osteoid thickness (p less than 0.05) during TD treatment. No effect on the trabecular bone volume was found. A reduction in the activation frequency of new remodeling sites and thereby a reduced bone turnover during TD treatment can explain the observed histomorphometric changes. The decrease in osteoid thickness may be related to the increased serum calcium concentration leading to better conditions for mineralization.

A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria.

33 normocalcemic patients (22 males and 11 females) aged 20-68 years with recurrent renal stone formation and idiopathic hypercalciuria were compared to 33 approximately sex- and age-matched normal controls. Quantitative histomorphometric analysis of iliac crest biopsies were performed after intravital tetracycline double labeling in the patients and in 30 sex- and age-matched normal controls. No difference was found between patients and controls in albumin adjusted serum calcium levels. Serum phosphorus was significantly reduced (p less than 0.01) in the patient group whereas the urinary phosphorus/creatinine ratio was increased (p less than 0.01). The serum calcium phosphate product (S-CaxS-P) was significantly reduced in the patients (p less than 0.05). As expected, the urinary calcium/creatinine ratio was higher in the patient group than in the controls (p less than 0.001). Serum parathyroid hormone was normal. The histomorphometric analysis revealed signs of a moderate mineralization defect (reduced adjusted appositional rate (p less than 0.05), prolonged mineralization lag time (p less than 0.05) and prolonged formation (p less than 0.05)), and an increased extension of eroded surfaces (P less than 0.05) in the patients. The amount of trabecular bone and the balance between the thickness of bone resorbed and later formed per remodeling cycle and all other histomorphometric parameters were found normal in the patients. The combined histomorphometric and biochemical data are best explained by a primary renal phosphate leak leading to hypophosphataemia and a slight mineralization defect. The hypercalciuria may be explained by an enhanced renal production of 1.25-dihydroxyvitamin D secondary to the reduced serum levels of phosphorus. No signs of secondary or primary hyperparathyroidism were observed.

Dietary factors in the pathogenesis and prophylaxis of calcium nephrolithiasis

A 47-year-old man, an executive at a financial institution, entered the hospital for the evaluation of recurrent nephrolithiasis and the spontaneous passage of a renal stone 3 months previously. The patient had been in good health except for a 15-year history of recurrent renal stones. The stones, which had occurred bilaterally, had been passed at a rate of 5 per year for the last 5 years; in the first 10 years he had passed a total of 5 stones. The patient had undergone cystoscopy with stone extraction on three occasions and recently had been treated with extracorporeal shock-wave lithotripsy for a partially obstructing stone in the left proximal ureter. Crystallographic analysis of these stones had revealed that were composed of 100% calcium oxalate monoand dihydrate. Radiography disclosed continuing stone formation by documenting the presence of new stones during the preceding 8 months. The patient had no history of gastrointestinal disease, excessive sun exposure, or current drug usage, including antacids and vitamin supplements. He had never received neck irradiation, nor had he experienced a urinary tract infection, His father and paternal uncle both had passed kidney stones of unknown type. The patient had undergone multiple evaluations for the cause of his stone diathesis but always had been told that all studies were normal. He was specifically told that hypercalcemia had never been detected. Review of his diet by a dietician showed that he usually consumed 110 g of protein/day, with an 80 g intake of animal protein. His calcium

Urinary Pyrophosphate in Patients with Recurrent Calcium Urolithiasis and in Healthy Controls: A Re-Evaluation

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals.In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1μmol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33μmol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus.We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.

Extracorporeal shock-wave lithotripsy: prevalence of renal stones 3-21 months after treatment.

One hundred and four (70%) of the first 148 patients who underwent extracorporeal shock-wave lithotripsy (ESWL) at the University of Florida were evaluated for persistent or recurrent renal stone disease. Radiographs obtained 3-21 months after treatment showed that 53 (50%) of 106 treated kidneys were free of stones. In 48 of the 53 kidneys that contained stones, the stones were residual fragments dating from the period immediately after ESWL. New stones had developed in only five kidneys. The 50% incidence of stone-free kidneys 3-21 months after ESWL is less than the 65-90% rate reported by other institutions in the United States and Europe. After stone removal by ESWL, new stone formation occurs at a rate of 5%, which is much lower than the expected recurrence rate of 37-50%.

Prevention of renal stones by a high fluid intake?

From the physiochemical view on the formation of urolithiasis a high fluid intake, provided it resulted in a high urine volume, should reduce the propensity of crystallization, crystal growth and stone formation. This critical review of the literature, however, demonstrates that there is little epidemiologic support for the hypothesis that a low urine volume is an important risk factor for renal stones in temperate climates. Few clinical studies have attempted to elucidate if a large diuresis can prevent further stone formation in a recurrent renal stone former. In the present study 115 recurrent stone formers were followed for an average period of 6 years without any other treatment than advice about a high fluid intake. The annual recurrence rate was around 23% but there was no difference between those who maintained a high urine volume and those who did not. Thus, the available evidence does not indicate that variations of fluid intake markedly affect stone formation.

Prevalence of renal stones in 60-year-old men. A 10-year follow-up study of a health survey.

Information on the occurrence of renal stones was obtained in a health survey of 50-year-old men and at follow-up of the same group 10 years later. At the latter investigation, 338 of 1781 participants (19%) had a history of renal stone formation. In 47% there had been recurrences. For the individual there was a continuous risk of acquiring a first renal stone up to the age of 60. Approximately 0.5% of the entire unselected population experienced onset annually up to this age. Recurrent renal stones occurred primarily in those with a positive family history of stones or early onset of stones, as well as in those who previously had frequently formed stones. A carefully obtained clinical history should be useful in predicting recurrences in the individual stone former.

Renal mass and reserve of vitamin D: Determinants in primary hyperparathyroidism

We studied circulating 1,25(OH)2D3 and its determinants in 102 patients with primary hyperparathyroidism (PHPT), 33 of them with recurrent renal stones, 60 with non-specific symptoms, and nine with overt bone disease. Means for serum 1,25(OH)2D3 and intestinal absorption of calcium were abnormally high in the renal stone group, slightly elevated in the non-specific group, and low-normal in the bone disease group. In the whole population of patients, we found a positive correlation between circulating 1,25(OH)2D3 and creatinine clearance (taken as an index of the functional renal mass). Negative correlations were observed between 1,25(OH)2D3 and age, and between creatinine clearance and age, the latter being not different from that observed in a normal large population. In the renal stone group, means for the determinants of the renal 1 alpha hydroxylase activity, that is, PTH activity expressed as nephrogenous cyclic AMP (NcAMP), serum phosphate and calcium were identical to those of the group with non-specific symptoms. However means for age were lower and functional renal mass significantly higher in the renal stone group, which may account for the higher value of circulating 1,25(OH)2D3. In the bone disease group, means for age, renal mass and serum calcium were identical to those of the group with non-specific symptoms, and NcAMP was far higher and hypophosphatemia more marked, which may not account for the lower value of circulating 1,25(OH)2D3. However, in the bone disease group, serum 25(OH)D was abnormally low, which may limit the renal production of 1,25(OH)2D3 and explain the low-normal circulating values.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of urinary sodium on calcium excretion in normal individuals

The twenty-four hour urinary excretion of calcium and sodium was measured in 38 normal volunteers after a week on a diet containing 400 mg of calcium per day. There was a significant correlation (P less than 0.001) between calcium and sodium excretion. The normal range of calcium excretion as a function of sodium excretion has been determined. This approach sharpens the definition of hypercalciuria by taking into account the influence of dietary sodium intake. It also removes the necessity of regulating dietary sodium as well as calcium intake before measuring calcium excretion in patients who form recurrent renal stones.

Renal tubular acidosis in recurrent renal stone formers.

Renal tubular acidosis (RTA) is a well-known metabolic disturbance that may promote recurrent renal stone formation. However, its incidence, screening criteria and association with other lithogenic metabolic abnormalities are not established in recurrent nephrolithiasis. 10 of 50 consecutive recurrent renal stone formers had a persistent fasting morning urinary pH above 6.0 and/or a basal plasma bicarbonate concentration below 20.0 mM. Acid and alkaline loads disclosed RTA in 3 patients: 1 patient had incomplete type-1 distal RTA in addition to hyperoxaluria; a second patient showed complete type-2 proximal RTA, hyperoxaluria and renal hypercaliuria; and a third patient had incomplete proximal RTA without any other metabolic derangement. These results reinforce the importance of RTA as an isolated metabolic abnormality among recurrent renal stone formers. In addition, RTA appears to be more commonly associated with other lithogenic metabolic derangements than has been previously suspected. The extensive metabolic protocol used in this study provides a useful tool in the diagnosis and therapeutic considerations of recurrent nephrolithiasis.

Hyperparathyroidism With Hypercalciuria and Urolithiasis: Long-Term Effects of Parathyroid Surgery and Postoperative Thiazide Therapy

Eleven hypercalciuric patients (10 women and 1 man) with hyperparathyroidism and recurrent renal stones are described. In 6 patients normal calcium metabolism was restored after the removal of a single adenoma. No new stones were passed during the follow-up period of 5 years. In 2 patients with more than 1 abnormal parathyroid gland, the hypercalciuria continued for 8–12 months after the parathyroid surgery. New stones developed in both of them. Subsequent thiazide therapy abolished the hypercalciuria and no additional renal stones were seen during a follow-up period of 4 years. In 3 patients hypercalcemia reappeared 2–12 years after parathyroid surgery. Treatment with thiazide decreased serum calcium and parathyroid hormone levels for at least 9–36 months. No new stones developed. Hypercalciuria and recurrent hypercalcemia appearing after parathyroid surgery for hyperparathyroidism and the responses to thiazide therapy are thought to be evidence for renal hypercalciuria. Thiazides are recommended as therapy in such patients to prevent the formation of new renal stones, and probably also the recurrence of hyperparathyroidism.

Limitations of the Oral Calcium Loading Test in the Management of the Recurrent Calcareous Renal Stone Former

Twenty-two patients with idiopathic hypercalciuria were evaluated using an oral calcium loading test and compared with 20 normal controls. Following a 12-hour overnight fast, all subjects collected a two-hour urine sample after which they received 1 g elemental calcium as galacto-gluconate in milk. Two further two-hour urine collections were obtained consecutively following the oral calcium load. In the fasting state, 4 (18%) of the 22 patients had urinary calcium excretion (UCaE) above normal, but none had elevated iPTH or urinary cAMP values. After calcium loading, only 10 (45%) of the 22 patients had delta UCaE greater than controls (delta = difference in UCaE between third and first urine samples). We conclude that despite demonstrable differences between the mean values of patient and control groups with respect to the UCaE following calcium loading, the large overlap of values negates the clinical usefulness of such procedures in the routine management of individual patients. The definition of renal leak hypercalciuria based on a high fasting UCaE alone remains of uncertain significance.

Hyperparathyroidism with hypercalciuria and urolithiasis: long-term effects of parathyroid surgery and postoperative thiazide therapy.

AbstractEleven hypercalciuric patients (10 women and 1 man) with hyperparathyroidism and recurrent renal stones are described. In 6 patients normal calcium metabolism was restored after the removal of a single adenoma. No new stones were passed during the follow‐up period of 5 years. In 2 patients with more than 1 abnormal parathyroid gland, the hypercalciuria continued for 8–12 months after the parathyroid surgery. New stones developed in both of them. Subsequent thiazide therapy abolished the hypercalciuria and no additional renal stones were seen during a follow‐up period of 4 years. In 3 patients hypercalcemia reappeared 2–12 years after parathyroid surgery. Treatment with thiazide decreased serum calcium and parathyroid hormone levels for at least 9–36 months. No new stones developed.Hypercalciuria and recurrent hypercalcemia appearing after parathyroid surgery for hyperparathyroidism and the responses to thiazide therapy are thought to be evidence for renal hypercalciuria. Thiazides are recommended as therapy in such patients to prevent the formation of new renal stones, and probably also the recurrence of hyperparathyroidism.

Ambulatory diagnostic evaluation of 389 recurrent renal stone formers. A proposal for clinical classification and investigation.

389 consecutive renal stone formers (275 males, 114 females) were investigated in an out-patient stone clinic. Renal tubular acidosis (RTA) was found in 83 patients (22%). Proximal RTA was twice as common as the distal tubular type. The acidification defects were exclusively of the incomplete form with normal basal blood acidbase status. Main diagnoses besides RTA were primary hyperparathyroidism (3.5%), medullary sponge kidney (3.5%), infection induced stones (3%), urate stones (2%), intestinal disorder (1.5%) and cystinuria (0.5%). The metabolic evaluation was mainly based on 24 h urine sampling on a free diet. In 248 patients (64%) no distinct abnormality was considered to be primarily responsible for stone formation. Clinical and biochemical analysis of these so-called idiopathic stone formers disclosed a male preponderance (80%) and, compared to a non-stone-forming control group, a higher urinary calcium excretion, yet with a considerable overlap between the two groups. Hyperuricosuria and hyperoxaluria were rare findings. The conclusion of the study is given as a proposal for clinical classification and ambulatory investigation of renal stone formers.

The mechanisms of hypercalciuria are unnecessary for treatment of recurrent renal calcium stone formers.

The mechanisms of hypercalciuria are unnecessary for treatment of recurrent renal calcium stone formers.

Seasonal Variation of Urinary Calcium and Oxalate Excretion, Serum 25(OH)D3 and Albumin Level in Relation to Renal Stone Formation

Seasonal variations in urinary calcium and oxalate excretion, serum 25(OH)D3 and albumin level were studied in 11 normo- and 11 hypercalciuric renal stone-formers, in 10 healthy subjects and in 14 long-stay hospital patients during one year. Serum albumin levels increased significantly during May--October in all four groups, whereas no significant changes occurred in serum calcium values when adjusted for differences in serum albumin concentration. Serum 25(OH)D3 level, urinary calcium and oxalate excretion were significantly higher during May--October than November--April in all except the long-stay hospital patients, whose corresponding values showed no seasonal changes and whose serum 25(OH)D3 levels as well as urinary calcium excretion were significantly lower than in the other three groups. The serum 25(OH)D3 level was significantly higher throughout the year in hypercalciuric than normocalciuric stone-formers. The hypercalciuric patients also passed more stones than the normocalciuric patients during a period of 9 years. There was a positive correlation between serum 25(OH)D3 and urinary calcium, between serum 25(OH)D3 and stone episodes and between urinary calcium and stone episodes. Because of this positive correlation, it might be useful to concentrate preventive therapy for recurrent renal stones to the light period only.

Kidney damage in recurrent renal lithiasis. A survey of 175 cases with clinicopathological observations.

We evaluated the degree of kidney damage in 175 patients treated by nephrectomy for recurrent renal stones. Renal histopathological lesions of the removed kidneys were graded and correlated to clinical and operative findings. Nonexcreting kidneys on intravenous pyelography or small atrophic kidneys with poor contrast excretion showing advanced hydronephrosis and pyelonephritic scarring intraoperatively corresponding to kidneys with advanced parenchymatous destruction histopathologically. In 91% of the cases severe renal damage was correctly predicted, and a decision to remove the affected kidney was justified.

DO THIAZIDES PREVENT RECURRENT IDIOPATHIC RENAL CALCIUM STONES?

In a double-blind controlled clinical trial 62 patients with recurrent idiopathic renal calcium stone formation were allocated either to treatment with bendroflumethiazide, 2·5 mg three times a day, or placebo. In each group the rate of stone formation during medication (average follow-up period 18 months) was compared with the rate of stone formation before medication (average control period 36 months). In both groups a striking fall in the rate of stone formation to the same level was found, indicating that thiazides in this study did not alter the spontaneous course of idiopathic renal calcium stone formation. It is doubtful whether life-long prophylaxis with thiazide is justified in patients with moderate rate of stone formation.

Is there a renal phosphorus leak in recurrent renal stone formers with absorptive hypercalciuria?

In ten male hypophosphataemic hypercalciuric recurrent renal stone formers with absorptive hypercalciuria and ten male normophosphataemic normocalciuric control persons, fasting plasma and urine chemistry was studied throughout the day under basal conditions and following an oral phosphorus load. After overnight fasting, plasma phosphorus and TMP/GFR were lower and urinary calcium higher in patients than in controls. Both in patients and controls, plasma phosphorus rose throughout the morning hours. In the afternoon, plasma phosphorus was almost equal in patients and controls. The circadian rise of plasma phosphorus despite no increase of urinary phosphorus argues against the presence of a fixed renal tubular phosphorus leak in absorptive hypercalciuria, at least in the fasting state. Patients differed from controls not only with respect to urinary calcium, but also with respect to fasting absolute and fractional urinary excretion of sodium and chloride. Increased fractional urinary sodium was found both in normotensive and hypertensive patients. Since tubular reabsorption of phosphorus and the setting of fasting plasma phosphorus depend, among other factors, on tubular handling of sodium, the finding may be relevant for the genesis of transient fasting hypophosphataemia in absorptive hypercalciuria.

Incidence and clinical importance of renal tubular defects in recurrent renal stone formers.

Renal tubular function was studied in 318 consecutive recurrent renal stone formers. Impaired acidification capacity was found in 19% of the patients, and tubular proteinuria in 13% of the patients. Most of the patients with defective acidification of the urine had the incomplete form of renal tubular acidosis (RTA), rpoximal and distal defects being equally common. The incidence of impaired acidification was much higher in the female (38%) than in the male (13%) stone formers. A further analysis of the clinical picture in patients with acidification defects revealed a more severe stone disease than among other stone formers. Characteristic findings were an early onset, multiple recurrences were an increased need for surgery. Stone analyses showed a high frequency of calcium phosphate stones. Investigations of renal tubular functions appear to be a valuable adjunct in the evaluation of recurrent renal stone disease.